Metabonomics analysis of liver tissues in d-galactosamine/lipopolysaccharide induced acute hepatic failure BALB/c mice

Background: Compared with biofluids, target tissues and organs may directly reflect pathophysiological state of a disease process. In this study, a D-galactosamine (GalN) / lipopolysaccharide (LPS) induced mouse model was constructed to investigate metabonomics of liver tissue and characterize direct changes of substance metabolism in acute liver failure (ALF). Methods: After pretreatment of liver tissue, gas chromatography coupled to time-of-flight mass spectrometry (GC/TOFMS) was used to separate and identify the liver metabolites. Partial least squares – discriminant analysis (PLS-DA) models were constructed to separate the ALF and control groups and to find those compounds whose liver levels differ significantly between the two groups. Results: Distinct clustering was observed between the ALF and control mice. Fifty-eight endogenous metabolites were identified. Compared with the control mice, many metabolites, including sugars, amino acids, fatty acids, organic acids, among others, underwent significant changes in ALF group, some of which differ from plasma levels. Significant reductions of some important intermediate metabolites indicate that production of ketone bodies, the tricarboxylic acid and urea cycles, gluconeogenesis, glycolysis and pentose phosphate pathways are inhibited after GalN/LPS administration. Conclusions: As a power technique, GC/TOFMS can be used to perform metabonomics study of liver tissue. GalN/LPS treatment can severely disturb substance metabolism in the liver different from that in the plasma.